Belantamab Mafodotin Fails to Meet PFS End Point in Relapsed/Refractory Multiple Myeloma

Belantamab mafodotin-blmf (Blenrep) did not generate a progression-free survival (PFS) benefit vs the combination of pomalidomide (Pomalyst) plus low-dose dexamethasone, failing to meet the primary end point of the phase 3 DREAMM-3 trial (NCT04162210).¹

At a median follow-up of 11.5 months for belantamab mafodotin and 10.8 months for pomalidomide plus low-dose dexamethasone, data showed that patients treated with belantamab mafodotin experienced a median PFS of 11.2 months compared with 7 months for pomalidomide plus dexamethasone (HR, 1.03; 95% CI, 0.72-1.47).

Additional data showed belantamab mafodotin elicited an overall response rate (ORR) of 41% vs 36% for pomalidomide plus dexamethasone. Notably, a very good partial response or better was achieved by 25% of patients in the belantamab mafodotin arm compared with 8% in the experimental arm. The median duration of response (DOR) was not reached (95% CI, 17.9–not estimable [NE]) for belantamab mafodotin vs 8.5 months (95% CI, 7.6-NE) for pomalidomide plus low-dose dexamethasone. The 12-month DOR rates were 76.8% and 48.4% for belantamab mafodotin and pomalidomide plus low-dose dexamethasone, respectively.

Data on overall survival (OS) reached 37.5% overall maturity at the time of data cutoff. The median OS was 21.2 and 21.1 months for belantamab mafodotin and pomalidomide plus dexamethasone, respectively (HR, 1.14; 95% CI, 0.77-1.68).

Data from DREAMM-3 are in the process of being shared with health authorities, according to a press release from GlaxoSmithKline. Discussions with health authorities are ongoing.

In August 2020, the FDA granted accelerated approval to belantamab mafodotin for the treatment of patients with relapsed/refractory multiple myeloma who have received 4 prior therapies, including an immunomodulatory drug, a proteasome inhibitor (PI), and an anti-CD38 antibody.² The regulatory decision was based on results of the phase 2 DREAMM-2 trial (NCT03525678).

The open-label, randomized DREAMM-3 trial evaluated the efficacy and safety of single-agent belantamab mafodotin compared with pomalidomide plus dexamethasone in patients at least 18 years of age with histologically or cytologically confirmed relapsed/refractory multiple myeloma who had undergone autologous stem cell transplant (ASCT) or were considered transplant ineligible, and had received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide and a PI, and must have documented disease progression on, or within 60 days of, completion of the last treatment or must be non-responsive while on last treatment.³

Other inclusion criteria included an ECOG performance status of 0 to 2, adequate organ function, and resolution of all prior treatment-related toxicities to grade 1 or lower, except for alopecia or grade 2 peripheral neuropathy. For patients who underwent prior ASCT, transplant must have been completed more than 100 days prior to initiating study treatment, and no active infections were permitted.

Key exclusion criteria included symptomatic amyloidosis, active POEMS syndrome, or active plasma cell leukemia; any systemic anti-myeloma therapy or use of an investigational drug within 14 days or 5 half-lives, whichever was shorter, before the first dose of study treatment; prior treatment with an anti–multiple myeloma monoclonal antibody within 30 days prior to first study treatment; prior BCMA-targeted therapy or prior pomalidomide treatment; prior allogeneic stem cell transplant; or any major surgery within 4 weeks of the start of study treatment.

Enrolled patients were randomly assigned 2:1 to 2.5 mg/kg of belantamab mafodotin monotherapy once every three weeks, or pomalidomide administered daily on days 1 to 21 of each 28-day cycle plus dexamethasone given once weekly on days 1, 8, 15, and 22 of each cycle.

The primary endpoint was PFS. Secondary endpoints included OS, ORR, DOR, assessment of minimal residual disease, and safety.

The safety and tolerability profile of belantamab mafodotin was consistent with the known safety profile of the agent. No new safety signals were identified. Rates of grade 3 keratopathy were consistent with previously reported data.

Ongoing studies are evaluating the efficacy and safety of belantamab mafodotin in combination with novel therapies and standard-of-care treatments in earlier lines of therapy and dosing optimization to maintain efficacy while reducing corneal events.

The phase 3 DREAMM-7 trial (NCT04246047) is investigating belantamab mafodotin plus bortezomib (Velcade) and dexamethasone vs daratumumab (Darzalex) plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma who received at least 1 prior multiple myeloma therapy.⁴

The phase 3 DREAMM-8 trial (NCT04484623) in examining belantamab mafodotin plus pomalidomide and dexamethasone vs bortezomib plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who had at least 1 prior line of multiple myeloma therapy including a lenalidomide-containing regimen.⁵

Data from DREAMM-7 and DREAMM-8 are expected to be reported in the first half of 2023.

References

1. GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma. News release. GlaxoSmithKline. November 7, 2022. Accessed November 7, 2022. http://bit.ly/3E7ze38
2. FDA approves GSK’s BLENREP (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma. News release. GlaxoSmithKline. August 6, 2020. Accessed November 7, 2022. https://bit.ly/3gxEXB1
3. Study of single agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone (pom/dex) in participants with relapsed/refractory multiple myeloma (RRMM) (DREAMM-3). ClinicalTrials.gov. Updated September 30, 2022. Accessed November 7, 2022. https://clinicaltrials.gov/ct2/show/NCT04162210
4. Evaluation of efficacy and safety of belantamab mafodotin, bortezomib and dexamethasone versus daratumumab, bortezomib and dexamethasone in participants with relapsed/refractory multiple myeloma (DREAMM 7). ClinicalTrial.gov. Updated September 26, 2022. Accessed November 7, 2022. https://clinicaltrials.gov/ct2/show/NCT04246047
5. Belantamab mafodotin plus pomalidomide and dexamethasone (Pd) versus bortezomib plus Pd in relapsed/refractory multiple myeloma (DREAMM 8). ClinicalTrial.gov. Updated October 14, 2022. Accessed November 7, 2022. https://clinicaltrials.gov/ct2/show/NCT04484623